Recently, we have demonstrated that electrical stimulation produces striking ultrastructural alterations in synapses of the cat superior cervical ganglion. Stimulation reduced the number of synaptic vesicles and enlarged the surface membrane of axonal terminals, while in recovery, synaptic vesicles reappeared and the surface membrane returned to normal dimensions. These findings suggest that vesicles become incorporated into the plasma membrane during transmitter release and subsequently reform from the plasma membrane. The objectives of the present research are to elucidate further the relationship between neural activity and synaptic ultrastructure, and especially, to characterize the functions of synaptic vesicles in cholinergic neural transmission. The in situ and in vivo perfused superior cervical ganglion of the cat will be studied by a combined electron microscopic and electrophysiologic approach. The time course of development of synaptic alterations and the time course of ultrastructural recovery from stimulation will be determined. Serial recostructions will be studied to determine the three dimensional surface and internal organization of stimulated and resting synapses. Synaptic ultrastructure will be studied in ganglia (a) chemically stimulated with elevated extracellular K ion concentrations, (b) electrically stimulated during blocked transmitter release, and (3) midly electrically stimulated in the presence of DNP. The effectiveness of stimulation and ganglionic transmission will be monitored by recording nictatating membrane contractions, which will be correlated with the ultrastructure of terminals. This research investigates fundamental ultrastructural correlates of synaptic function, which is basic to all brain function, and may have relevance to a physical basis of memory.